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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic corticosteroids have been recommended as a therapeutic option in patients with moderate to severe COPD. In an early stage of the disease, i.e. chronic bronchitis with mild or no airflow obstruction, a trial with inhaled steroids could reveal potential benefits, particularly in terms of a modulation of airway inflammation. We therefore investigated the effect of inhaled fluticasone (1000 microg day(-1)) on markers of airway inflammation in 19 patients with chronic bronchitis (mean+/-SEM FEV1, 83.4+/-3.0% predicted; FEV1/VC, 67.5+/-2.4%) in a double-blind, cross-over, placebo-controlled manner. Visits were performed before and after two 4-week treatment periods. separated by a 4-week washout period. Lung function, the concentration of exhaled nitric oxide, differential cell counts in induced sputum and the number of cells positive for iNOS, as well as the levels of LDH, ECP, neutrophil elastase and IL-8 in sputum supernatants were determined. Although the total cell number decreased significantly after fluticasone (geometric mean 12.3 vs. 7.7 x 10(6)/ml; P<0.05) it was not significantly different from the change observed after placebo (14.2 vs. 10.6 x 10(6)/ml; n.s.). None of the other parameters showed statistically significant changes after fluticasone or placebo and the results did not depend on the presence of airway hyperresponsiveness. We conclude that in patients with chronic bronchitis short-term treatment with inhaled corticosterids did not improve lung function or inflammatory parameters to an extent which was statistically significant as compared to spontaneous variability.
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PMID:In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation. 1121 7

The effects of two vasoactive agents (adenosine A2A agonist, CGS 21680, and adrenoceptor agonist, noradrenaline) were examined on cardiac output (CO), heart rate (HR), blood pressure (BP), mean circulatory filling pressure (Pmcf), resistance to venous return, arterial resistance, dP/dt, plasma levels of NO2-/NO3-, and inducible nitric oxide synthase (iNOS) activity in lungs ex vivo, following treatment with tumour necrosis factor-alpha (TNF-alpha; 30 microg/kg) in anaesthetized rats. Treatment with TNF-alpha produced significant reduction in CO (41+/-2%), dP/dt (26+/-3%), BP (26+/-2%) and Pmcf (27+/-4%; n=6; mean+/-SEM), but increased arterial resistance. There were no significant changes in the plasma levels of NO2-/NO3-levels over time following treatment with TNF-alpha, but there was a significant increase (approximately twofold) in the activity of the iNOS in the lungs of animals treated with TNF-alpha. Administration of CGS 21680 (1.0 microg/kg per min) significantly increased CO (44+/-6%), HR (12+/-2%), Pmcf (24+/-4%) and dP/dt (24+/-5%) in TNF-alpha-treated rats. CGS 21680 also significantly reduced arterial resistance (33+/-2%) without altering resistance to venous return in TNF-alpha-treated rats. While noradrenaline (1.0 microg/kg per min) infusion did not significantly increase CO, it did significantly increase HR (12+/-1%), BP (55+/-9%), Pmcf (47+/-5%), dP/dt (65+/-7%), resistance to venous return (64+/-20%), and arterial resistance (41+/-16%) in TNF-alpha-treated animals. The reduction in BP due to administration of TNF-alpha is the result of significant reduction in CO. Consequently, the decline in CO can be attributed to a combination of a negative inotropic effect as well as a reduction in Pmcf. It is evident that infusion with CGS 21680 could reverse the negative impact of TNF-alpha on CO by increasing dP/dt, Pmcf and HR as well as a reduction in arterial resistance. The fact that noradrenaline did not significantly increase CO in TNF-alpha-treated rats can be attributed to increased arterial resistance as well increase in resistance to venous return.
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PMID:The influence of tumour necrosis factor-alpha on the cardiovascular system of anaesthetized rats. 1128 46

A number of previous studies have indirectly (electron paramagnetic resonance, nitrite/nitrate, ribonuclease protection assay for inducible nitric oxide synthase (iNOS) mRNA, l-citrulline assay) demonstrated the production of nitrogen monoxide (NO) during early cardiac allograft rejection. This study reports the first direct, quantitative measurement using an electrochemical method of NO produced from rejecting allograft tissue studied in vitro. A rat heterotopic abdominal transplant preparation was utilized. Day 7 isograft (ACI to ACI) or allograft (Lewis to ACI) transplanted hearts were atraumatically harvested and suspended at 4 degrees C in Ringers-Hepes solution. An electrochemical system highly sensitive and specific for NO consisting of a Nafion-coated platinum disk electrode (lower limit, 50 nM NO) coupled to an analysis system measured ongoing oxidation of NO. Measurements were carried out after inserting the electrode in the tissue block and warming the block to 25 degrees C. Additional measurements were also made after incubation of tissue with aminoguanidine (AG), a relatively selective iNOS inhibitor. Direct measurements (mean +/- SEM) from allograft tissue indicated a fourfold increase in NO as compared with isografts (13.41 +/- 4.40 microM NO vs. 3.43 +/- 2.04 microM NO). Incubation of allograft tissue with AG reduced NO levels to isograft levels (13.41 +/- 4.40 microM NO vs. 5.94 +/- 3.14 microM NO); AG had no effect on measured isograft NO levels. Direct, quantitative measurement of NO from tissue is feasible and reproducible, and discrimination between different levels of NO production can be made. These results confirm the imputed results from the previous studies using this experimental model. This technology promises to be a valuable tool for evaluating specific modulators of NO production studied under a variety of physiologic and pathophysiologic conditions.
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PMID:In situ measurement of nitric oxide production in cardiac isografts and rejecting allografts by an electrochemical method. 1173 Mar 63

We examined whether brain damage after focal cortex trauma may be attenuated by adenoviral delivery of the glial cell line-derived neurotrophic factor (GDNF) gene. For this reason, injections of vehicle, of an adenoviral vector deleted in the E1 region (Ad-dE1) or a vector expressing the GDNF gene from a CMV promoter (Ad-GDNF) were stereotactically placed in the rat sensorimotor cortex, and one day later cold lesions of the cerebral cortex were induced. Lesions were associated with pronounced brain swelling one day after injury. The degree of brain swelling was significantly attenuated by Ad-GDNF delivery (Ad-GDNF: 7.4 +/- 2.2%, Ad-dE1: 21.1 +/- 4.9%, vehicle: 20.9 +/- 5.0% of contralateral; mean +/- SEM, P < 0.05). Furthermore, Ad-GDNF treatment resulted in a significant reduction of the lesion volume seven days after lesioning (Ad-GDNF: 21.8 +/- 2.8 mm3, Ad-dE1: 44.1 +/- 1.6 mm3, vehicle 40.9 +/- 8.6 mm3, P < 0.05). The decrease in the lesion size was associated with a reduction in the number of inducible nitric oxide (iNOS)(+), activated caspase-3(+) and DNA fragmented cells in the perilesion rim, as revealed by immunocytochemistry and terminal transferase biotinylated-dUTP nick end labeling (TUNEL). In Ad-GDNF-treated animals, the number of caspase-3(+) and TUNEL(+) cells was also reduced in the lesion-remote thalamus. The present study shows that adenoviral GDNF delivery is protective in focal cortex trauma.
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PMID:Adenovirus-mediated glial cell line-derived neurotrophic factor (GDNF) expression protects against subsequent cortical cold injury in rats. 1174 92

Administration of tumour necrosis factor-alpha (TNF-alpha) produces progressive reduction in cardiac output (CO) by affecting preload, afterload and cardiac contractility. We have examined the effect of an endothelin receptor antagonist, tezosentan (1, 3 or 10 mg/kg), on CO, heart rate (HR), blood pressure (BP), mean circulatory filling pressure (P(mcf)), resistance to venous return (RVR), arterial resistance (AR), dP/dt, stroke volume (SV), plasma levels of NO(2)(-)/NO(3)(-), and inducible nitric oxide synthase (iNOS) activity in lungs, ex vivo, following treatment with TNF-alpha (30 microg/kg) in anaesthetized rats. Treatment with TNF-alpha alone resulted in significant reduction in CO (40+/-4%), dP/dt (24+/-2%), P(mcf) (24+/-2%), BP (21+/-3%) and SV (38+/-5%) ( n=6; mean +/- SEM), and significant increases in RVR (38+/-9%) and AR (45+/-6%). There were no significant changes in HR or in plasma levels of NO(2)(-)/NO(3)(-) in animals treated with TNF-alpha but there was a modest but significant increase in iNOS activity. Tezosentan alone did not have any effect on haemodynamics, plasma levels of NO(2)(-)/NO(3)(-) or iNOS activity. Tezosentan at the highest dose abolished the effects of TNF-alpha on dP/dt, AR, and RVR. In animals treated with a combination of TNF-alpha and highest dose of tezosentan CO, P(mcf), BP, and SV were reduced by 28+/-5%, 16+/-3%, 21+/-4%, and 27+/-5%, respectively. Tezosentan was able to inhibit the negative impact of TNF-alpha on AR and dP/dt but not on P(mcf). It is likely that the negative impact of TNF-alpha on CO in tezosentan-treated animals could be entirely attributed to reduction in preload.
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PMID:Haemodynamic effects of endothelin receptor antagonist, tezosentan, in tumour necrosis factor-alpha treated anaesthetized rats. 1259 57

Sildenafil citrate (Viagra) is the most widely used drug for treating erectile dysfunction in men. We recently demonstrated that it induces potent protective effects against ischemia-reperfusion (I-R) injury in rabbit hearts through the opening of mitochondrial ATP-dependent K+ channels. In the present study, we investigated the role of the NO-dependent signaling pathway in delayed cardioprotection by sildenafil. Adult male ICR mice were treated with saline or sildenafil (0.7 mg/kg IP) 24 hours before global I-R in the Langendorff mode. Infarct size was reduced from 27.6+/-3.3% in saline-treated control mice to 6.9+/-1.2% in sildenafil-treated mice (mean+/-SEM, P<0.05) without compromising cardiac function. Reverse transcription-polymerase chain reaction revealed a transient increase in endothelial and inducible NO synthase (eNOS and iNOS, respectively) mRNA in sildenafil-treated mice, peaking at 45 minutes (eNOS) and 2 hours (iNOS) after sildenafil injection. The magnitude of mRNA increase was more pronounced for iNOS than for eNOS. In addition, a significant increase in both iNOS and eNOS protein was detected 24 hours after sildenafil treatment. A selective inhibitor of iNOS, 1400W (10 mg/kg IP given 30 minutes before I-R), abolished sildenafil-induced protection (23.7+/-2.8%, P<0.05 versus sildenafil). These data suggest that the induction of NO synthase isoforms is an essential component of the signaling mechanism for sildenafil-induced delayed preconditioning. However, iNOS appears to be the primary isoform that mediates the robust cardioprotection.
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PMID:Sildenafil induces delayed preconditioning through inducible nitric oxide synthase-dependent pathway in mouse heart. 1263 71

We have previously shown that inhibition of nitric oxide generated by inducible nitric oxide synthase (iNOS) results in impaired colon anastomotic healing. Therefore, we proceeded to assess whether disruption of iNOS activity alters the normal pattern of growth factor expression during anastomotic healing. Two groups of male Sprague-Dawley rats underwent distal colonic division and anastomosis, jugular venous catheterization and subcutaneous placement of polyvinyl alcohol sponges. The first group (n = 10) received q8 hour intravenous injections of 10 mg/kg L-N-iminoethyl-lysine (L-NIL, a selective inhibitor of iNOS), while the second group (n = 12) received equal volumes of saline. On postoperative day 5, animals were sacrificed and anastomotic bursting pressure was determined. Histologic sections of the anastomosis were subjected to in situ hybridization versus mRNA of the proteins listed below. Positive controls were reacted with a poly-thymidine (poly-T) probe versus ubiquitous mRNA poly-adenine tails. Positively stained cells were quantified using a calibrated optical grid encompassing 0.5 mm(2) area centered over the anastomosis. Results are reported as the number of positive cells per 1000 cells positive for poly-T. L-NIL treated animals demonstrated an 18% decrease in wound fluid NO(X) compared to controls (29.2 +/- 1.2 vs. 34.6 +/- 2.0 microM, mean +/- SEM; P = 0.035). This corresponded to a 17% decrease in anastomotic bursting pressure (153 +/- 4 vs. 182 +/- 8 mm Hg, mean +/- SEM; P < 0.05). L-NIL also markedly increased the number of cells expressing transforming growth factor-beta, tumor necrosis factor-alpha, vascular endothelial growth factor, and both inducible and endothelial forms of nitric oxide synthase. L-NIL had no effect on the expression of basic fibroblast growth factor. The data demonstrate that iNOS inhibition markedly disrupts the profile of cytokine and growth factor mRNA normally expressed during anastomotic healing. This provides in vivo evidence that NO modulates gene expression during anastomotic healing.
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PMID:Modulation of growth factor and cytokine expression by nitric oxide during rat colon anastomotic healing. 1265 65

Ketamine and xylazine (K/X) are commonly used in combination as an anesthetic agent in experimental animal models. We previously noted that K/X attenuated lipopolysaccharide (LPS)-induced liver injury, gastric stasis, and reduced symptoms of endotoxemia. Because ketamine attenuates expression of several proinflammatory genes, we examined the effects of K/X on inducible nitric oxide synthase (iNOS), which has been implicated in endotoxin-induced tissue injury. We hypothesized that K/X would attenuate LPS-induced expression of iNOS in various organs in the rat. Rats were given either intraperitoneal saline or ketamine (70 mg/kg) and xylazine (6 mg/kg) 1 h before saline or LPS (20 mg/kg). Rats were sacrificed 5 h later and stomach, duodenum, jejunum, ileum, colon, liver, lung, kidney, and spleen were collected for determination of iNOS protein immunoreactivity by Western immunoblot. Data reported in densitometric units (DU) as mean +/- SEM (n >/= 5; ANOVA). LPS significantly increased iNOS protein immunoreactivity in all tissues examined versus saline controls (P </= 0.05, all groups). K/X significantly attenuated LPS-induced iNOS protein immunoreactivity in all of the aforementioned organs (P </= 0.05, all groups). Furthermore, K/X almost completely blunted LPS-induced expression of iNOS in stomach, duodenum, jejunum, and colon. These data indicate that K/X attenuates LPS-induced upregulation of iNOS in a variety of tissues. Furthermore, in rat models studying the in vivo effects of endotoxin, especially those evaluating the gastrointestinal system, careful consideration needs to be given if the anesthetic combination of K/X is used, as it alters LPS-induced expression of iNOS, an important pathophysiologic mediator in endotoxemia.
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PMID:Ketamine/xylazine attenuates LPS-induced iNOS expression in various rat tissues. 1287 36

Nitric oxide has various biological activities including smooth muscle relaxation, anti-inflammatory activity, anti-coagulatory activity. As the human placenta is known to express nitric oxide synthases, this study investigated the possible effect of labor on the expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in human placental tissues at term. Both eNOS and iNOS mRNA expression in placental tissues in labor were significantly higher than those in the amnion, chorion laeve, decidua vera and myometrium. The eNOS mRNA and protein expressions in placental tissues in labor (n = 12) were 1.6023 +/- 0.1652 (eNOS/GAPDH, mean +/- SEM) and 12.8 +/- 1.3 arbitrary units (AU), respectively, which were similar to those not in labor (n = 10), 1.5806 +/- 0.2042 (eNOS/GAPDH) and 11.4 +/- 1.8 AU. The iNOS mRNA and protein expressions in the placental tissues in labor were 1.2831 +/- 0.2436 (iNOS/GAPDH) and 10.7 +/- 2.1 AU respectively, similar to those not in labor, 1.9254 +/- 0.8004 (iNOS/GAPDH) and 13.3 +/- 1.8 AU. The guanosine 3',5'-cyclic monophosphate (cGMP) concentration in the placental tissues in labor was 23.6 +/- 1.4 fmol/g wet tissue, similar to that not in labor, 26.1 +/- 2.0 fmol/g wet tissue. These findings suggest that nitric oxide production in the human placenta is maintained during labor.
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PMID:Expression of nitric oxide synthase isoforms in the human placenta is not altered by labor. 1461 9

Ischemia-reperfusion injury plays a major role in graft dysfunction following transplantation. Extensive research has demonstrated that nitric oxide (NO) plays a fundamental role to protect the heart against this injury. Consequently, we quantified NO synthase (NOS) isoform protein levels in a rat heart transplant model during short and prolonged reperfusion following ischemia. Experiments were performed using a modified Lewis to Lewis heterotopic abdominal heart transplantation with a total ischemic time of 3 hours followed by 1 or 24 hours of blood reperfusion (n = 12). Heart function, as represented by the rate pressure product, increased from 7912 +/- 489 to 27067 +/- 9982 mm Hg/min (mean +/- SEM, short vs prolonged reperfusion, P = .0027). NOS isoform protein levels determined using Western blotting of freeze-clamped hearts were compared to baseline values. eNOS protein levels were significantly lower during short reperfusion compared to the basal value (P = .0077) or to prolonged reperfusion (P = .004), returning to the basal value after 24 hours of reflow. iNOS protein was not detected in the basal condition or after 1 hour of reflow, but was present after 24 hours of reflow (P = .0001 vs basal value and 1-hour reflow). nNOS protein was 69% lower after 1 hour of reflow compared with the baseline value (P = .0001), it was not restored after 24 hours of reflow (P = .002). These results suggest involvement of the NO pathway in ischemia-reperfusion injury with distinctive roles of NOS isoforms during short and prolonged reperfusion following ischemia.
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PMID:Modulation of the NO pathway during short or prolonged blood reperfusion following ischaemia in a heterotopic rat heart transplantation model. 1525 12


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